tbuckley/cabot-search huggingface dataset:
Gut microbiota profiling and clinical response in patients with metastatic non-small cell lung cancer receiving endothelial growth factor-tyrosine kinase inhibitors (EGFR-TKI).
Authors: Jing Zhao, Jie Rao, Qianxia Li, Lin Yang, Guangyuan Hu
Journal: Journal of Clinical Oncology (2023)

e21050 Background: Pre-clinical mouse models have suggested that gut microbiota in immune relates with inflammation and modulates tumor response, while it remains uncertain in lung cancer patients with EGFR mutation. We aimed to evaluate the relationship between gut microbiota and early tumor response after EGFR-TKI treatment in metastatic non-small cell lung cancer (NSCLC) patients. Methods: NSCLC patients haboring EGFR exon 19del or 21L858R mutation were enrolled in this study in Tongji Hospital, Wuhan, China. Early response was assessed at 12 weeks after EGFR-TKI initiation per RECIST 1.1, and patients were categorized as responders (CR+PR) and non-responders (SD+PD). Stool sample was collected prior to EGFR-TKI treatment. The V3–V4 region of the 16S rRNA gene was amplified for the characterization of the gut microbiota profiling. Data were analyzed on the online tool of Majorbio Cloud Platform to compare microbiota community structure and abundance at α- and β-diversity levels. Linear discriminant analysis with effect size (LEfSe) was used to to identify biomarkers using a taxonomic bar chart. PICRUSt2 was used to predict the functional profiling of microbial communities. P-values &lt; 0.05 were considered statistically significant. Results: From June 2020 to Sep 2022, 24 patients were included. CR, PR, SD and PD were recorded in 2 (8.3%), 14(58.3%), 6(25%) and 2(8.3%) patients, respectively. The four most abundant bacteria at phylum level were Firmicutes (64.4%), Bacteroidota (15.1%), Proteobacteria(14.7%), and Actinobacteriota (4.6%). The relative abundance of Actinobacteriota counts were significantly higher in responders than those with no-responders ( p= 0.032). There was a significant difference in the Sob index (α-diversity) between responders and no-responders (60.062 vs. 86.250, p= 0.043). β-diversity was similar between the two groups ( p= 0.087). Differential analysis using LEfSe identified that genus Rothia was significantly enriched in responders; phyla Actinobacteria and Deinococcota, genera Ruminococcus, Collinsella, Holdemanella were significantly enriched in non-responders. PICRUSt2 based on KEGG prediction identified that Transketolase and Carbamoyl-phosphate synthase were significantly enriched enzymes in non-responders compared with responders, the p values were 0.019 and 0.022, respectively. Conclusions: The early response of EGFR-TKI was associated with alteration of specific genera and metabolic function of gut microbiota. Further research with larger cohorts is needed to validate this pilot study. [Table: see text]
From abstract to publication: Factors predictive of publication success in the field of breast and gynecological malignancy.
Authors: Ankita Kapoor, Arya Mariam Roy, Sanjana Aggarwal, Simrat Gill, Kristopher Attwood, Anthony George, Yagya Ahlawat, Asha Gandhi, Riya Jayesh Patel, Harshit Kapoor, Mazen Jizzini, Maithreyi Sarma, Shipra Gandhi
Journal: Journal of Clinical Oncology (2023)

e23007 Background: Cancer research has rapidly evolved over the last few decades which has led to an improvement in patient care and outcomes. Dissemination of this research presented at meetings is essential to inform clinical practice. However, there continues to be a delay in the publication of data even after successful presentation of research as abstracts. In our study, we aim to determine abstract characteristics associated with successful peer-reviewed publication after presentation at the American Society of Clinical Oncology (ASCO) annual meeting for Breast and Gynecological malignancies. Methods: All oral abstracts (OA) &amp; poster abstracts (PA) presented in the Breast &amp; Gynecologic cancers categories from 2017/2018 ASCO annual meetings were included in the retrospective study. Manuscript publication was confirmed by searching PubMed using a data cut-off of December 2022. Publication characteristics like number of authors, time to publication (in months (mo)), study size, nature of results, impact factor, gender, H-index, citation of first author (FA) &amp; last author (LA), NIH funding of LA were collected. Univariate logistic regression modeling was used to measure the association between publication status and select predictors. Results: 40/50 (80%) OA &amp; 246/527 (46.6%) PA were published in PubMed indexed journals. Mean time to publication for OA was 17.41 mo &amp; for PA was 19.52 mo. Mean IF for published OA was 28 &amp; PA was 9.98. Of presented abstracts, 30/50 (60%) OA &amp; 313/527 (59.39%) PA had positive results. Of the ones published, 23/40 (57.5%) of OA (p=0.72) &amp; 190/246 (77.2%) of PA (p&lt;0.001) had positive findings. 250/527 (49.14%) PA &amp; 17/50 (33.3%) of OA were presented by females. Of the published OA, 15/40 (37.5%) had female FA &amp; 10/40 (25%) female LA. For published PA, FA females were 118/246 (47.9%) while LA females were 86/246 (34.9%). For published PA, median H-index for FA was 33 &amp; LA was 68. 16/40 (40%) LA of published OA &amp; 62/246 (25%) of published PA had NIH funding. Conclusions: Our study reveals that poster abstracts with positive findings are more likely to be published, implying publication bias in research. In addition, there is also higher likelihood of publication if last author is NIH funded. Our study highlights the need to address these factors to maximize the chances of publication of impactful research. [Table: see text]
Treatment at twilight: Is less more in the management of octogenarians with non-small cell lung cancer (NSCLC)?
Authors: Ethan Burns, Sunil Mathur, Ryan Blair Kieser, Wan Hsiang Chen, Eric Bernicker
Journal: Journal of Clinical Oncology (2023)

9042 Background: Treatment of advanced/metastatic NSCLC in older patients is hindered by performance status, comorbidities, and treatment toxicities. Moreover, whether multiagent chemotherapy in combination with immune checkpoint inhibitor (ICI) therapy outweighs a conservative approach is controversial. This study aims to assess treatment patterns and outcomes in patients ≥80 years with NSCLC through data provided by the national cancer database (NCDB). Methods: Adults ≥80 years with stage III/IV NSCLC, available treatment data, and diagnosis between 2015-2018 were included. Patients were stratified by therapy including none, ICI alone, chemotherapy alone, and chemotherapy+ICI; radiation and surgical management was also assessed. Median overall survival (OS) was evaluated by Kaplan-Meier survival methods, and differences were assessed by hazard ratios (HR) and 95% confidence intervals (CI). The mean difference in OS was compared between systemic therapy arms. Pearson Chi-Squared tests assessed the significance of treatment differences, with a p-value of &lt; 0.05 considered statistically significant. Results: There were 42,356 patients included; 29,698 (70.1%) had stage IV disease and 26,314 (62.1%) had adenocarcinoma. A total of 3,248 (7.7%) received ICI, 11,505 (27.2%) received chemotherapy, 2,393 (5.6%) received chemotherapy+ICI, and 25,210 (59.5%) received no therapy. Median OS for no therapy, ICI, chemotherapy, and chemotherapy+ICI was 2.63 (95% CI: 2.57, 2.69), 10.68 (95% CI: 9.96, 11.39), 12.35 (95% CI: 11.98, 12.72), and 14.03 (95% CI: 13.87, 14.88) months, respectively. Compared to no therapy, ICI alone (HR: 0.377 [95% CI: 0.361, 0.393], p = 0.000), chemotherapy alone (HR: 0.439 [95% CI: 0.426, 0.452], p = 0.000), and chemotherapy+ICI (HR: 0.345 [95% CI 0.328, 0.363], p = 0.000) improved OS. Compared to ICI, chemotherapy and chemotherapy+ICI had a longer mean OS difference of 2.48 (95% CI 1.82, 3.13) (p &lt; 0.001) and 1.9 (95% CI 1.01, 2.78 (p &lt; 0.001) months, respectively. In chemotherapy alone, the median OS was 1.12 months (95% CI: 0.55, 1.70) (p &lt; 0.001) longer with multiagent vs single agent. There was no difference between chemotherapy vs chemotherapy+ICI (0.57 months [95% CI: 0.16, 1.31], p = 0.234), or for ICI+single agent vs ICI+multiagent (0.67 months [95% CI -1.18, 2.54], p = 1.00). Treatment with radiation (HR: 0.664 [95% CI: 0.649, 0.679], p &lt; 0.001), primary-sit(HR: 0.495 [95% CI: 0.465, 0.527], p &lt; 0.001) and non-primary surgery (HR: 0.867 [95% CI: 0.811, 0.927], p &lt; 0.001), and receipt of ICI vs no ICI (HR: 0.912 [95% CI 0.873, 0.954], p &lt; 0.001) improved OS. Conclusions: Patients ≥80 years with NSCLC derived most benefit from multiagent chemotherapy or chemotherapy+ICI, with no OS difference between ICI+single or ICI+multiagent therapy. ICI alone and no therapy had inferior OS. Future trials to corroborate this finding would benefit the elderly population.
Using patient-reported outcomes to assess the impact of germline genetic testing on prostate cancer patients.
Authors: Sarah M. Nielsen, Neal D. Shore, Mukaram Gazi, Christopher Michael Pieczonka, Sean Heron, David J Cahn, Laurence Belkoff, Aaron D. Berger, Brian Mazzarella, Joseph Veys, David Morris, Richard Bevan-Thomas, Alexander Engelman, Paul Dato, Robert Cornell, David R Wise, Mary Kay Hardwick, Brandie Heald, Robert Luke Nussbaum, Edward D. Esplin
Journal: Journal of Clinical Oncology (2023)

10607 Background: Germline genetic testing (GGT) affords prostate cancer (PCa) patients (pts) opportunities for targeted therapies, prevention and cascade testing. Patient-reported outcomes (PRO) can evaluate physician effectiveness in promoting patient test comprehension and clinical decision making, which are critical to realize the benefits of GGT. PROs from a large PCa GGT study among urologists were analyzed. Methods: A prospective study enrolled unselected PCa pts from 15 primarily community urology practices. Pts underwent 84-gene GGT, with PROs collected via electronic or paper surveys &gt;1-month post GGT. Differences in proportions were determined using two-tailed Fisher’s exact test and significance was set at &lt;0.05. Results: PROs were completed by 561/982 (57%) pts (85% white, 82% non-metastatic, median age at testing 70 years). 59 (11%) pts had positive results, 247 (44%) negative and 255 (46%) variants of uncertain significance (VUS). 72% accurately recalled their result (range, 50% [VUS]-93% [negative]). 66% of positive pts, 80% negative and 54% VUS correctly understood if their result was associated with cancer risk or not. 72% of positive pts had or planned to complete ≥1 physician recommendations, significantly more than negative or VUS pts (Table). Most pts reported that their test result reduced their concerns (40%) or did not impact their level of concern (52%) regarding their PCa diagnosis, treatment or followup. 19% of positive pts reported increased concern. Conclusions: GGT for PCa was deployed without causing undue concern and resulted in adherence to physician recommendations. Still, there is room for improvement in how test results (especially VUS) and recommendations are communicated to pts. [Table: see text]
The impact of neighborhood socioeconomic deprivation on clinical trial enrollment at an NCI-designated cancer center.
Authors: Amina Dhahri, Madison Ginn, Benjamin Daniel Powers, Aman Chauhan, John L. Villano, Lowell Brian Anthony, Ralph Zinner, Reema Anil Patel, Zhonglin Hao, Lovoria Williams, M. Cecilia Monge B., Susanne M. Arnold
Journal: Journal of Clinical Oncology (2023)

e18614 Background: Previous studies showed that SES is a barrier to cancer clinical trial enrollment. But, few studies have investigated the impact of socioeconomic deprivation (SED) on trial participation using a granular geocoded measure. To overcome this gap, we assessed trial enrollment at the only NCI-designated cancer center in Kentucky. Methods: We conducted a retrospective study of patients enrolled in GI and lung cancer trials from 2012 to 2021 using the Area Deprivation Index (ADI), a validated dataset that ranks census block groups based on SED and includes 17 variables. Patients with an identifiable state and national rank ADI were included and stratified in quintiles. Chi-square and Kruskal-Wallis tests were used for analysis. Results: We included 1130 patients who enrolled in a trial; 10 patient refused enrollment 0.9%. Trial participation by gender was similar: 50.5% female and 49.5% male. Race included White 93.5%, African American 5.7% and Asian 0.71% patients. Hispanics made 0.5% of the cohort. When assessed by national ADI, 45% of clinical trial participants were in the highest ADI quintile. When assessed by ADI state ranking, there was similar distribution in trial enrollment. Enrollment at the national and state levels were significant for age (p &lt; 0.001, for both) and race (p = 0.003 and 0.023, respectively). Conclusions: Prior studies have shown that low SES is a barrier trial enrollment; however, this study demonstrates that using a granular measure of SED at the state level, GI and lung cancer clinical trial enrollment has similar distribution by ADI quintiles. But, when assessed at the national level, 45% of trial participants were in the highest SED quintile. This highlight the importance of state and national-level comparisons for SED and suggest that future research is needed to identify barriers and facilitators of cancer clinical trial enrollment. [Table: see text]
Efficacy of teclistamab in patients (pts) with heavily pretreated, relapsed/refractory multiple myeloma (RRMM), including those refractory to penta RRMM and BCMA (B-cell maturation antigen) directed therapy (BDT).
Authors: Priyanka Venkatesh, Shebli Atrash, Barry Paul, Omar Alkharabsheh, Aimaz Afrough, Zahra Mahmoudjafari, Muhammad Umair Mushtaq, Hamza Hashmi, James A. Davis, Al-Ola A. Abdallah
Journal: Journal of Clinical Oncology (2023)

e20044 Background: Teclistamab is a B-cell maturation antigen (BCMA) targeting bispecific agent approved in 10/2022 for pts with relapsed refractory multiple myeloma (RRMM) based on the results of the MAJESTEC-1 study. This is the first report on the real-world safety and efficacy of teclistamab in pts with RRMM and highlights patterns of utilization and outcomes in pts, including those who would have been ineligible for enrollment on MAJESTEC-1. Methods: Twenty-two pts with RRMM who received teclistamab at the University of Kansas Health System as of 2/10/2023 had electronic medical records (EMR) reviewed retrospectively in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). Baseline pt characteristics were outlined by descriptive analyses. Responses were evaluated using the International Myeloma Working group (IMWG) criteria. Adverse events were graded based on the CTCAE v5.0 criteria. Results: Pts included in the analysis had received a median of 6 prior LOT and 64% had extramedullary disease (EMD). All of the pts were triple class exposed and 91% were triple class refractory, 77%/59% were penta-class exposed/refractory, while 72% were refractory to prior BCMA directed therapy (BDT). Median follow up was 3.1 (1.7-4.1) months. The most common grade III/IV hematological toxicities were lymphopenia (95%), neutropenia (36%), leukopenia (36%), thrombocytopenia (32%) and anemia (9%). Cytokine release syndrome (CRS) was observed in 9 (41%) pts, all o which were grade I/II events, while immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 5 (23%) pts, with 2 (9%) pts having grade III events. The overall response rate was 50%, and was 56%,46% and 28% for pts who were BDT refractory, penta- refractory, or had EMD, respectively. Of those that did respond, responses tended to be deep (73% ≥ VGPR; 55% ≥ CR). No treatment related mortality was observed, although5 (23%) pts died due to disease progression during follow up. Conclusions: Our study demonstrates the efficacy of teclistamab in heavily pre-treated RRMM, including those who were penta-refractory, BDT refractory, or had EMD. Overall, teclistamab was well tolerated with no major safety events. Keywords: Plasma cell disorders, relapsed multiple myeloma, Penta-class refractory myeloma, BCMA directed therapy. [Table: see text]
A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy.
Authors: FangJie Liu, Bo Qiu, DaQuan Wang, Rui Zhou, PengXin Zhang, ShiYang Zheng, JinYu Guo, QiaoTing Luo, SuPing Guo, Hui Liu
Journal: Journal of Clinical Oncology (2023)

e20569 Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.
Effects of different immune microenvironment characteristics on predictive efficacy of <i>PTCH1</i> mutations in immune checkpoint inhibitor therapy of solid tumors.
Authors: Guangyu Zhu
Journal: Journal of Clinical Oncology (2023)

e21026 Background: The PTCH1 gene encoding the protein corticosteroid receptor, which regulates the activity of the Sonic Hedgehog (SHH) signaling pathway. Mutations in PTCH1 result in disruption of the SHH signaling pathway and are closely related to the development of various solid tumors. Previous research has shown that mutations of the PTCH1 gene may result in decreased of antigen expression on the surface of tumor cells. However, relevant correlation with the efficacy of ICI therapy and immune microenvironment are still lacking. Methods: NGS data from an independent cohort (the MSKCC study cohort) of 1661 patients and Chinese clinical dataset (panel on 381/733-gene) of 35337 patients with pan-cancer to explore the association between PTCH1 mutations and immune biomarkers. TMB was defined as total number of somatic non-synonymous mutations in coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (Dako 22C3). Patients from three independent cohorts (OAK, POPLAR and MSKCC study cohort) and were used to analyze the correlation between PTCH1 mutations and the efficacy of immune checkpoint blockade immunotherapies (ICIs). Estimation of immune filtration cells scores were conducted via TIMER2.0 (http://timer.cistrome.org/). Results: In Chinese cohort, there were 1384 (3.91%) patients harboured PTCH1 mutation ( PTCH1 mut ), slightly more than the MSKCC cohort (2.52%, 42/1661). For the TMB, both Chinese (median, 24.14 Muts/Mb vs 8.52 Muts/Mb, P ＜0.0001) and MSKCC (median, 22.30 Muts/Mb vs 5.90 Muts/Mb, P = 0.0035) cohort were associated with higher TMB than the wild-type. Supplemental analysis of MSI in the Chinese cohort showed significant differences between the PTCH1 mut and PTCH1 wt groups (P ＜0.0001), but not on PD-L1 levels (P = 0.64). In terms of prognostic effect with ICIs therapy, PTCH1 mut were significantly associated with the overall survival (OS) of NSCLC (median, 5 months vs 11 months; HR = 1.61; 95% CI, 1.00-2.60; P = 0.049) and colorectal (median, 11 months vs 8 months; HR = 0.27; 95% CI, 0.08–0.90; P = 0.023). Interestingly, PTCH1 mut in NSCLC was inversely associated with ICIs efficacy, as opposed to other solid tumors. Exploring the correlation between PTCH1 and immune microenvironment, it was found that CD4+ T cell (P＜0.001), macrophages (P＜0.001), NK cells (P＜0.001), and CD8+ T cells (P = 0.015) infiltration was significantly positively correlated in colorectal. But the infiltration of most immune cells was negatively correlated with PTCH1 mut in NSCLC, that the B cells (P = 0.005), macrophages (P = 0.049), and NK cells (P = 0.022) had a significant difference. Conclusions: The results showed that the PTCH1 had a high correlation in solid tumors with TMB and MSI. The PTCH1 might a potential biomarker for ICIs therapy, and the immune microenvironment may be a factor affecting of it.